Project Summary: New funding for analyses of novel inflammatory, surfactant disfunction, oxidative stress, and fibrosis biomarkers within these exhaled breath condensate (EBC) samples could synergistically advance our understanding of oxidative lung injury with relatively modest financial investment. We will synergize existing virtual consortia (parent R01 & an ionizing radiation (IR) exposure cohorts) by adding two new trans- disciplinary laboratory-focused investigators from the host institutions (Sullivan & Kondrashova). Svendsen will lead the resulting joint epidemiological analyses. Our immediate goal is to identify reliable biomarkers of oxidative lung injury that are reproducible, have reference values and provide information on the underlying oxidative processes. Our long-term goal is to develop new translational countermeasures of latent adverse lung effects of oxidative hazard exposures (e.g. Cl2, IR) within disaster populations. We believe that pulmonary surfactant alterations may be a feasible option for further biomarker study and potential countermeasure development. We will test the overall hypothesis that inactivation of surfactant is the primary mechanism associated with the observed oxidative lung injury that best explains the lung function changes rather than fibrotic mechanisms. In two oxidative lung injury cohorts, we will assess novel biomarkers in archived EBC samples from previous health screenings in 2005 and 2008-2010. This will position us to compete for new funds for analysis of the parent R01 EBC samples where we can study additional potential progressive disease mechanisms and oxidative stress biomarkers observed 7-10 years after the first EBC collection and relate them to new comprehensive pulmonary diagnostic testing data (diffusing capacity, impulse oscillometry, plethesmography, 6-minute walk, eNO, spirometry, pre/post bronchodilator spirometry, EBC pH). This will expand the impact of the parent R01 dramatically by allowing us to link the functional measures with their potential corresponding mechanisms. We will contrast the same EBC biomarkers between two oxidative lung injury cohorts: one in the USA led by Dr. Sullivan (Cl2) while the other in Ukraine led by Dr. Kondrashova (137Cs ionizing radiation). Results from each parallel set of studies will advance the science of both chlorine and ionizing radiation-induced lung injury independently. By performing such studies synergistically with identical protocols we can contrast disease mechanisms across exposures, and generate broader knowledge of lung injury mechanisms and biomarkers. If our overall hypothesis is true, then our research will have a large impact on the understanding of oxidative lung injury. Unlike fibrotic mechanisms, mitigation of surfactant disfunction may be possible with additional pharmacological development. This study could help expedite development of novel countermeasures and subsequent public health interventions for those thousands currently suffering.